PhD Smart CAR-T cell therapy for Neuroblastoma

The Wienke Group is seeking an enthusiastic and highly motivated PhD candidate.

The Institute

The Princess Máxima Center for Pediatric Oncology in Utrecht is the national research hospital concentrating healthcare, research, and education for pediatric cancer. The institute aims to provide the highest level of care for all children with cancer and has the ambition to cure all children of cancer with an optimal quality of life. The center brings together the best possible care and scientific research, creating a unique interdisciplinary institute for pediatric oncology in Europe. We have top-notch core facilities and laboratory resources, including a Data and Trial Center, Flow Cytometry facility, Single Cell genomics core, Microscopy and Imaging core, High-throughput Screening facility, Protein facility, and Organoid Technology core and Big Data core. Immunotherapy development has become an important strategic focus within the center, with a brand new in-house cell therapy facility scheduled to open this year.

The Wienke group

Our group aims to translate immunological insights in the tumor microenvironment of pediatric solid tumors into clinically applicable therapeutic interventions, with a focus on improving (CAR-)T cell therapy to overcome cell therapy failure. We apply multi-omics of the tumor microenvironment (including single-cell sequencing, proteomics, spectral flow cytometry, imaging mass cytometry, high-dimensional live cell imaging) to understand mechanisms of immunotherapy failure and treatment escape. With these insights, we generate innovative (CAR-)T cells to improve their efficacy by advanced engineering methods.

The position

This project focuses on overcoming a recently uncovered immune evasion strategy of solid tumors: hijacking neuronal factors (e.g. neuropeptides, neurotrophins) to suppress immune responses. Neuroblastoma is infamous for its secretion of neuronal factors. Neuroblastoma is a solid childhood tumor arising from neural crest cells, with a poor prognosis and overall survival of less than 50% in patients with high-risk disease. New therapeutic interventions are thus direly needed. CAR-T cell therapy has promise, but is still failing in many patients, and neuronal factors are thought to play a crucial role.

First we will identify which neuronal factors play a key role in suppressing CAR-T cells. In collaboration with our bioinformatician you will analyze single-cell RNA sequencing data of neuroblastoma and other solid tumors to create an in-depth atlas of the T cell-neuronal factor interactions and prioritize the most promising neuronal targets for therapeutic intervention. Target identification will be aimed at both undermining tumor immune evasion and increasing the anti-tumor activity of immune cells. Neuronal targets will be validated by mass-spectrometry and functionally in vitro (with tumor organoids). Subsequently we will use high-throughput drug screens to identify drugs inhibiting neuronal factors, which can synergize with CAR-T cell therapy. Moreover, you will develop novel CAR-T cells genetically modified to withstand suppression by neuronal factors. We have access to different neuroblastoma model systems (e.g. organoids, mouse models) to validate newly identified therapeutic strategies in vitro and in vivo.

Education and skills

We are looking for a highly driven, ambitious candidate with a master’s degree in Medical Biology, Life Sciences or in a related field and a background in (cancer) immunology/immunotherapy. Since this PhD will encompass both ‘dry’ lab (i.e. bioinformatics) and immunological ‘wet’ lab (e.g. cell culture, CAR-T engineering, flow cytometry, killing assays) work, previous experience with both will be greatly appreciated. This position requires good command of both oral and written English, excellent communication and organization skills, as well as the ability to work within a dynamic group.

Our job offer

A temporary, full-time PhD position for a total duration of 4 years (36 hours/week), in an ambitious and dynamic team. You will initially be contracted for a period of 1 year, after which your performance will be evaluated, and the contract may be extended for the remaining years. The Princess Máxima Center operates according to the collective labor agreement ‘cao algemene ziekenhuizen’. Your gross monthly salary will be in FWG 45-6 and will include an 8,33% gross monthly salary holiday allowance and 8,33 % end-of-year bonus.

How to apply

You can apply for this position until the 25th of August 2025 by pressing the orange apply button on this screen.

Please provide:

• an up-to-date resume/CV
• a short motivation letter describing your background and interests (max. 2 pages)
• contact information of 2 references

For more information, please contact Dr. Judith Wienke.

Acquisitie naar aanleiding van deze vacature wordt niet op prijs gesteld.